Aging means all the physiological changes of a body occurring by the lapse of time and the aging aspects and speed differ in each individual case and are affected by numbers of reasons. Even in an individual, aging shows different aspects in each organ, so that individual oriented study on aging has a limitation. More particularly, the functions of each organ and tissue are changed by aging, which is caused by the change of cell function. For example, the damage of nerve cells of brain causes the decrease of recognition, the damage of subcutaneous fat cells causes the loss of the elasticity of skin, the loss of melanin generating capability of melanocytes of hair root causes white hair, etc. So, the aging in an individual is caused by the aging of cells of the individual. Thus, recently, the study on aging has been focused on the cell-basis study. After all the efforts made by numbers of scientists to explain aging completely, the exact mechanism of aging has not been disclosed yet because of its various aspects and complexity. Just some theories on aging have been brought forward through phenomenological studies. Among them, an oxygen free radical theory and a telomere theory are given consequence. The former says that the accumulated oxidative stress resulted from oxygen free radicals generated during normal metabolism process is the major reason of aging and the latter says that a telomere located in the end of a chromosome gradually disappears after repeated cell division, resulting in the stop of cell division and cell death in the end. Other theories are also mutual assistant to give a full explanation on aging. More precisely, regarding an oxygen free radical theory, an oxygen free radical generated during normal metabolism process destroys cell components such as a lipid, a protein, a sugar or a DNA randomly, causing oxidative stress to a cell or a tissue, by which it causes not only in variety of diseases such as cancer, cardiovascular diseases such as cerebral apoplexy and arteriosclerosis, chronic inflammatory diseases such as rheumatism, respiratory diseases, autoimmune diseases, etc (Halliwell, B and Gutteridge, J. M. C, Biochem. J., 1984, 219, 1-14; Freeman, B. A. and Grapo, J. D., Lab Invest, 1982, 47, 412-426; Ames, B. N., Science, 1983, 221, 1256-1264; Fridovich, I., Arch. Biochem. Biophys., 1986, 247, 1-11; Vishwanath, M. S., Nutrition in Clinical Practice, 1995, 10, 19-25), but also aging to death by accumulating such oxidative damages for a long time. The oxygen free radical theory on aging was first proposed by Harman in 1956 (Harman, D., Free radical theory of aging, Alan R Liss, New York, 1936, 3-49), since then, numbers of experiments have given results supporting the theory. As an example, life span lengthened by controlling basal metabolic rate (BMR), that is, oxygen consumption, by restricting a diet or by restricting movement (Medvedev, Z. A., Biol. Rev., 1990, 65, 375-398; Loe, J., Northrop, J. H., J. Biol. Chem., 1971, 32, 103-121; Sohal, R. S., Insect aging, Springer-Verlag, Heidelberg, 1986, 23-44; Sohal, R. S., Aging, 1982, 5, 21-24).
In order to protect a living body from oxidative damages, the living body has anti-oxidant substances and anti-oxidant enzymes such as superoxide dismutase (SOD), catalase or peroxidase. But, their defensive power against oxygen free radicals becomes weaker, as getting old (Orr, W. C. and Sohal, R. S., Science, 1994, 263, 1128-1130; Sohal, R. S. et al., J. Biol. Chem., 1995, 270, 15671-15674). For example, the activity of SOD separated from an old mouse was lower than that of a young mouse. Especially, life span of a fruit fly lengthened over 30% by increasing the activity of anti-oxidant enzymes, SOD and catalase, suggesting that oxygen free radical is closely connected with aging. Therefore, anti-oxidant agents that are able to remove oxygen free radical or to inhibit lipid peroxidation can be effectively used for the treatment of diseases caused by oxygen free radical and for the prevention of aging.
The lasting exposure on oxidative stress caused by harmful environment such as air pollution, UV, stress or diseases, increases radicals in a living body, creates wrinkles by destroying hyaluronic acid, elastin, collagen and a connective tissue of corium, and even causes diseases like dermatitis, pimples or skin cancer by destroying cells by oxidizing lipid in cell membrane. The radicals are related to the generation of melanin, being a reason of discoloration, freckles and wrinkles. As of today, ascorbic acid, alpha-tocopherol or SOD have been used for making skin protective cosmetics or medical supplies as a free radical eliminator. But, the price is high and the effect thereof is doubtful owing to the instability of the chemical mixture. Therefore, it is a common goal in the industries of medical supplies, food and cosmetics to develop a substance that is safe and has satisfactory effect of removing a free radical.
Telomere theory is the other major theory explaining aging. A normal cell of human goes through only determined numbers of cell division in vitro. That is, cell division is stopped after completing the scheduled division, which is called replicative aging. Telomere theory explains why such replicative aging is taking place (Kim, S. K., et al., Oncogene 21: 503-511 (2002); Harley, C. B., et al., Nature 345: 458-460 (1990); Olovnikov, A. M. J. Theoret. Biol. 41: 181-190 (1973); Harley, C. B., Exp. Gerontol. 27: 375-382 (1992); Allsopp, R. C., Weissman, I. L., Oncogene, 21: 3270-3273 (2002)). Telomere is a terminal part of linear chromosome of eukaryotes and has a very unique structure in which ‘TTAGGG’ sequence is repeated. Especially, guanine (G) forms a very stable G-quartet structure by hydrogen bond, so that it stabilizes and protects a chromosome (Moyzis, R. K., et al., Proc. Natl. Acad. Sci. 85: 6622-6626 (1988)). Telomeres in Human somatic cells, though, have been known to be shorten little by little every time cell division takes place (Harley, C. B., Futcher, A. B., Greider, C. W., Nature 345: 458-460 (1990); Harley, C. B. et al., Exp. Gerontol. 27: 375-382 (1992); Allsopp, R. C., Weissman, I. L., Oncogene 21: 3270-3273 (2002)). This is because of the “end replication problem”, meaning that when DNA is replicated, the primer region of 3′-end is not replicated (Olovnikov, A. M. J. Theoret. Biol. 41: 181-190 (1973)). Thus, every time cell division takes place, a replicated DNA becomes shorter as much as the part of primer and so does a telomere in a chromosome. As the telomere continues to be shorter beyond critical point, single and double strands of DNA are cut off, resulting in that cell division is tied up in G1 stage by cyclin dependent kinase inhibitors (Harley, C. B., et al., Exp. Gerontol, 27: 375-382 (1992)). According to the recent study, the length of a telomere varies with oxidative stress. That is, oxidative stress accelerates the shortening of a telomere, which is because that the oxidative damage in the telomeric DNA part is less recovered than other parts of a chromosome (Saretzki, G., von Zglinicki, T., Ann. New York Acad. Sci. 959: 24-29 (2002); von Zglinicki, T., Ann. New York Acad. Sci. 908: 99-110 (2000); von Zglinicki, T., TRENDS Biochem. Sci. 27: 339-344 (2002); Lorenz, M., et al., Free Radic. Biol. Med. 31: 824-831 (2001)).
Based on those theories on aging, the present inventors have endeavored to find a novel substance from plants to inhibit skin aging. Plants have a well-established self-defense system to protect themselves from oxidative stress caused by lots of oxygen free radicals including superoxide radical, a residual product of photosynthesis. So, plants themselves are important sources for an anti-oxidant agent. Thus, the present inventors have investigated a radical scavenging activity and a lipid peroxidation inhibiting activity with 350 species of plants, and have selected a few candidates having an anti-oxidant activity. Considering easiness in securing resources and not being discovered about its components and activity, the present inventors have chosen Cercis chinensis as a final candidate for an anti-oxidant agent.
Cercis chinensis, a deciduous shrub, belongs to Leguminosae family and is native to China. It is 3-5 m tall and has no fluff on its twigs but has many lenticels. It has simple alternate leaves, which shape into a round heart, 6-11 cm in diameter, not fluffy and plain and smooth on the edge. The upper part of a leaf is dark green and glossy, but the back of the leaf is light green. Stipules are quadrangle and fall early. A flower is 1-2 cm long and a leaf axil has many blossoms. There is no rachis but a peduncle. A calyx has a bell shape and 5 blunt saw teeth on the upper edge. A corolla is butterfly-shaped and has magenta color. It has 5 irregular petals. It has 10 stamens that are all separated. The stamen base is attached in a calyx and a filament is thin and long. It has a single pistil. An ovary is glossy without a fluff. It has a hag, too. The upper style is bent and the stigma is small, short and plain. The flowering time is about April and leaves are out after blossom. As a legume, a fruit has a flat band shape whose end part shrinks to form a short bill. A pod is 7-12 cm long and ripens in August or September. A seed is round, flat and close to black (Lee, Y. N., Flora of Korea, Kyo-Hak Publishing Co., Ltd., Seoul, 1996, 362-363). The stem bark, root bark and stem of C. chinensis have been used to promote blood circulation, dysmenorrhea, edema, bruising and various injuries (Bae, K. H., The medicinal plants of Korea, Kyo-Hak Publishing, Seoul, Korea, 2000).
The present inventors have completed this invention by confirming that an extract of Cercis chinensis, unlike other synthesized anti-oxidant agents, is harmless to human, has an excellent cell protecting activity against oxidative stress and can even lengthen the life span of a cell by slowing the shortening speed of a telomere, so that it can be effectively used as a cosmetic composition for anti-aging, protection of skin elasticity and wrinkle care.